Age-related differences in metabolism and cerebral blood flow (rCBF), as measured by positron emission tomography (PET), were enhanced in frontal cortex when young and old subjects received sensory activation. Dorsal vs. ventral patterns of rCBF activation during face and location matching were similar in young and old subjects, but young subjects had more activation of occipital cortex and older subjects had more frontal activation. Activation of rCBF in during working memory was predominantly in frontal cortex in younger subjects and in parietal cortex in older subjects. Significant sex differences existed in age-related effects on regional brain metabolism in the temporal and parietal lobes, Broca's area, thalamus and hippocampus. A patient with autopsy proven Parkinson's disease had a metabolic pattern indistinguishable from that seen in DAT. Subjects with Turner syndrome (45,X) had reduced volume of the hippocampus, lower parietal metabolism and impairment of visuospatial abilities. Clinically distinct subgroups of DAT patients, one with prominent visual symptoms and one with frontal lobe features, were compared to typical DAT patients and found to have characteristic metabolic patterns, with occipital and frontal lobe hypometabolism, respectively. There is a distinctive cognitive profile in fragile X syndrome that is distinct from other forms of mental retardation and distinctive metabolic pattern, involving elevation in subcortical brain regions.